Isolation of quinoline from a mixture of nitrogen bases



U Nl-aT ED iso oa'orgomho mn FnoM A Mix- I TURE OE NITROGENB'ASES Karl H. EngeIQ Teane'ck, N;lJ.,--assi-gnor to Allied Chemical '&'-Dye- Corporatiom'New York, N. Y.,

a corporation of'Ne'wXork No Drawing. Applicationj June 27, 1945, Serial No. 601,937

This invention relates to the separation of quinoline from mixtures thereof with other nitrogen bases. This application is acontinuation-in-partof'application Serial'No; 346,347, file'dl July 19; 1940; now- Patent- No." 2-,'408',975', dated October- 8, 1946'.

Quino'line'is customarily extracted along with othefnitrogen bases from coke oven distillates and other sources of'heterocyclic nitrogen bases by"m'ea'ns' of an aqueous solution of a mineral acid, usually sulfuric acid. After liberation of the' base's fro'mthese acid solutions by'means of alkali;- the base 'mixtui'es thus obtained are customalrily fractionally distilled to obtain fractions predominating in a particular base Byfraci347" tionatingtar bases liberated from u n-011119- con'taining oil, fractions predominating" in quinoline maybeobtainemin some casesia'relatively' wide-boiling fraction, e. g. one having a boiling range 015233" to 240 C., may be separated yin'other'cases, a close-cut fraction, e. g. one-having a'boiling range 237.5 to- 239.5 C., is taken. Quinoline fractions as ordinarily produced heretofore might contain as 'much as 80% to'92% quinoline, the remainder consisting of other'nitrogen bases of boiling range close to quinolin'e-and'not readily separable by distillation, e. g. trimethylanilines, isoquinoline, quinaildinegand other bases. Mixtures of this kind have found limited practical applications and are o'f -loweconomic'vame. Pure quinoline, however, is a product of great commercial intrest, for example; in the preparationof its derivatives, especially pharmaceutical products and dyes. Purequinoline 'is becoming of particular importance at'present'since 'it is a suitable starting material fofthe-prepatratiori of nicotini'c' acid, a'member of the vitamin B complex.

I have discovered that phosphoric acid forms an" acid p'lriols'phate (CI-ItNl-EPOU of limited water solubility andthat this phenomenon may be employed to effect separation of substantially pure quinolin'e from" other nitrogen bases with which it maybeadmixed. Off such other bases, I have found that isoquinoline, which may form an appreciable partof the impurities in the quinoline fractions, formsa phosphate that is extremely'soluble'in water. Quinaldine, on the other h'and, I have found; for-ms a'p'hosphate having;a watersolubility"substantially" the same as a that o'i quinoli-nephosphatej hence; a crude frac tion treated with'phos'phoric' acid fb'f'recovery' of quinoline should contain relatively small amounts of quinaldine; not-over- 5'%', andpreferably less-than m ny-weight:

it-claims. (omen-48s) 2, Quinoline'fractions treated in'accordance with my invention for're'covery ofquinoline may have a quinoline content of as low as about 70%. Preferably, however, in order to obtain a fraction containing not more than 5% quinaldine, preferably less than 2%, the crude quinoline fraction should be subjected to reasonably close fractional distillation-to obtain a fraction containing from 80% to 92% quinoline. In accordance with this invention, such fractions are caused to react with phosphoric acid in the presence of an aqueous medium. Preferably, an amount of phosphoric acid corresponding to the stoichiometric amount required to react with all the bases present is used; an excess of phosphoric acid over and above the stoichiometric amount may beused, if desired. The amount of water'present should besuch as to retain in solution substantially all of the nitrogen bases present except the-quinoline and to avoid undue solution of quinoline phosphate.

In a preferred method of carrying outthis invention, a predetermined amount of phosphoric acid is added to a crude quinoline fraction and the temperature of the reaction mixture permitted to rise. After all the phosphoric acid has been added, precipitation of the quinoline phosphate is effected by cooling the reaction mixture to a temperature within the range of 0 to 305' C., lower temperatures being advantageous as the solubility of the phosphate decreases substantially on cooling; The quinoline phosphate thus preferentially precipitated is separated from the dissolved phosphates and other bases by filtration, or by centrifuging, and washing, preferably with cold water, or with water containing a" few percent of phosphoric acid or of monosodium phosphate to reduce the solubility of quinoline phosphatek p The washed quinoline phosphate may be dried to produce crystal quinoline phosphate containing no water of crystallization, Thereshltant productwhich' is in the form of clean crystals" is a useful product for direct use. commerciallyv for the manufacture of quinoline derivatives. Free quinolinemay be obtained by hydrolyzingf the quinoline phosphate. For example, quinoline phosphate or a solution thereof may be treated with an aqueous alkaline material, such as caustic soda, lime or ammonia. The freed ,quinoline may be further purified by dehydration and distillation'.

Ordinary commercial gradesof phosphoric acid may'be used to' precipitate the" quinoline phosphate. Mo'noor'di'sodium phosphate with thequinoline phosphate. about 55 C., the mass being cooled with agitation with water, dried, and distilled. refined quinoline were obtained having a melting point of 1'7.1 C. and {a purity of 95.6%.

- 3 equivalent sulfuric acid may be used, however, instead of the more expensive free phosphoric I acid, i. e. the phosphoric acid may be formed in situ. Most advantageously, alkali phosphate recovered after liberation of the quinoline from tity of precipitated quinoline phosphate.

The following examples are illustrated, of, the

" process of my invention. All parts are by weight. boiling range 236.6" to 237.8" C. and a specific gravity of 1.09 at 25 C. containing 91.5% quinoline, 4 isoquinoline, .5 quinaldine, and approximately 4% othernitrogen bases were suspended in 500 parts water, and 520 parts of 85% phos phoric acid were gradually added, dissolving the quinoline. The temperature of the solution rose to 80 C. due to the generated heat of neutralization. This solution was cooled to about C. While being agitated.v Quinoline phosphate (C9H7N.H3PO4) precipitated in small but Wellfor-med crystals. The reaction mixture was filtered by suction and washed with 300 parts of water at about 10 C., successive small portions being applied to the crystals. On a dry basis, 641 parts of quinoline phosphate were thus obtained. I

-The quinoline phosphate thus obtained was purified by suspending it, without drying, in 1000 parts of water. To remove traces of hydrocarbon oils, the solution of quinoline phosphate may be heated to boiling and partially evaporated; alternatively, the aqueous mixture may be subjected to steam distillation to drive off the hydrocarbon oils. Quinoline was liberated from the phosphate solution by adding a solution of 150 parts of sodium hydroxide in 300 parts of water, the mixture stratified, the upper quinoline layer separated and washed with water, residual water removed by distillation, and the quinoline thus obtained distilled. The material thus recovered boiled at 237.5 to 237.? Cghad a melting point of -15.9 C. and purity of 98.2% quinoline.

Example '2.-300 parts of crude quinoline; fraction boiling in the range of 2325" to 240.5 0., having a specific gravity of 1.089 at= C. and

containing, approximately 81% quinoline, were added to a solution formed by adding-300 parts of monosodium phosphate (NaH2PO4.H2O), 800 parts of water and 110 parts of concentrated sulfuric acid (94%). A clear solution resulted.

Traces of hydrocarbon oils of the same boiling range as the quinoline fraction were removed ,from this solution by evaporating it until 200 parts of. water had been distilled oif. The resultant solution was cooled to induce precipitation of the Crystallizationbegan at to about 20 C. p 4

The crystal slurry was filtered on a suction filter and the crystals washed with successive portions of an aqueous solution containing 5% monosodium phosphate to remove adhering mother liquor, a total of 400' parts of the solution being used for this purpose. The quinoline phosphate was suspended in 500 parts of water and the quinoline liberated by adding a solution of sodium hydroxide in amount suflicient to convert the The sodium phosphate solution was regenerated by the addition of a quantity of sulfuric acid equivalent to the sodium hydroxide used in libcrating the quinoline. The thus regenerated solution may be cyclically reused in the treatment of a further batch of crude quinoline The mother liquor from the quinolinephosphate which contains the phosphates of other nitrogen bases present in the crude quinoline, besides a small proportion of quinoline, may be mixed with sodium hydroxide suflicient to liberate these bases.

The pure dry quinoline had a clean, sweet odor andremained light-colored for an extended time in contrast to the crude material which had a pungent odor and discolored rapidly after distillation.

Since certain changes may be made in carrying out the above process without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and notin a v limiting sense. 1

Iclaim: q

l. In a process for separating quinolineirom; a mixture thereof with closely-related, like boiling nitrogen bases, in which mixture quinolineconstitutes at least 70% by Weight of the total bases present and in which quinaldine is present only in relatively small amounts, the step that comprises treating the mixture in the presence of water with a quantity of phosphoric acid sufficient to react with a substantial portion of the nitrogenbases to precipitate quinoline phosphate from an aqueous solution of the mixture, the amount of -water present being sufficiently high to retain in solution substantially all the nitrogen bases except quinoline, and 'sufiiciently low to cause substantial precipitation of quinoline phosphate.

2. In a process for separating quinoline from a nitrogen base mixture containing at least 70% quinoline, not over 5% quinaldine, and isoquinoline; the steps that comprise treating the mixture in the presence of water with a sufficient quantity of phosphoric acid to react with a substantial proportion of the nitrogen bases present to precipitate quinoline phosphate from the mixture, and separating the precipitated phosphate the amount of water present being sufiiciently high to retain in solution substantially all the nitrogen bases except quinoline, and suificiently low 7 to cause substantial precipitation ;of quinoline phosphate. 7 V

3. In a process for separating quinoline from a nitrogen base mixture containing from' 80,% to 92%;,quinoline, less than 2% quinaldine, andiso. quinoline, the steps that comprise treating the mixture in the presence of water with a suificient quantity of phosphoric acid to react with substantially all the quinoline present -tojprecipitate quinoline phosphate from the mixture; and sepa.- rating the precipitated phosphate, the amount of water present being sufiiciently high to retain in solution substantially all the nitrogen bas'esexcept quinoline, and sufiiciently low .to'cause substan the nitrogen bases except 'quinoline;;-an d sumaciently low to cause substantial precipitation of quinoline phosphate, heating the resultant mixcure to remove therefrom traces of hydrocarbon oils of the same boiling range as the quinoline fraction, cooling to precipitate quinoline phosphate, separating the quinoline phosphate from the resultant slurry, and converting the separated phosphate to free quinoline.

KARL H. ENGEL.

REFERENCES CITED UNITED STATES PATENTS Name Date Pickhardt Feb. 21, 1882 Number Number Name Date 2,035,583 Bailey Mar. 31, 1936 2,288,281 Huijser et a1 June 30, 1942 2,309,324 McAilister Jan. 26, 1943 2,408,975 Engel Oct. 8, 1946 FOREIGN PATENTS Number Country Date 22,139 Germany Apr. 1883 285,666 Germany July 1915 570,675 Germany Feb. 18, 1933 OTHER REFERENCES Chemiker-Zeitung, (1901), pp. 280 and 281. Hoogewerff et a1. Recueil des travaux chimiques des pays-Bas., vol. 4, (1885) page 125.

Certificate of Correction Patent No. 2,456,774. December 21, 1948.

KARL H. ENGEL It is hereby certified that errors appear in the printed specification of the above numbered patent requiring correction as follows:

Column 3, line 11, for the Word illustrated read illustrative; line 13, before boiling insert Example 1.500 parts of crude quinolc'ne of;

and that the said Letters Patent should be read with these corrections therein that the same may conform to the record of the case in the Patent Oflice.

Signed and sealed this 12th day of April, A. D. 1949.

THOMAS F. MURPHY, I

Assistant OomMz'ssz'oner of Patents. 

